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mGLU Receptors pp 225–239Cite as

Regulation of Hippocampal mGluR-Dependent Long-Term Depression by GluA2-Dependent Cofilin-Mediated Actin Remodeling

Part of the The Receptors book series (REC,volume 31)

Abstract

The AMPA glutamate receptors (AMPARs) are the principal mediators of the fast excitatory synaptic transmission, and they are important for various forms of synaptic plasticity. The GluA2 subunit of AMPARs is particularly interesting because it controls a number of key properties of AMPARs, including Ca2+ permeability and receptor trafficking. In this chapter, we will discuss the critical involvement of GluA2 in mGluR-dependent long-term depression (mGluR-LTD) at the hippocampal CA1 synapse. We will summarize the data showing that GluA2 is essential for the expression of mGluR-LTD, but interestingly, the contribution of GluA2 in this form of LTD requires GluA2 N-terminal domain and its interaction with N-cadherin. In addition, we will evaluate the role of cofilin and its upstream regulator LIMK1 in mGluR-LTD and associated spine plasticity. Finally we will discuss interactions between GluA2 and LIMK1/cofilin and propose a molecular model to coordinate structural and functional plasticity through GluA2-dependent, cofilin-mediated actin remodeling.

Keywords

  • mGluR-LTD
  • Spine
  • GluA2
  • Actin
  • Cofilin
  • N-cadherin
  • Structural and functional plasticity

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Acknowledgments

This work was supported by grants from the Canadian Institutes of Health Research (CIHR, MOP119421, ZPJ), Canadian Natural Science and Engineering Research Council (NSERC, RGPIN341498, ZPJ), CIHR, and China Joint Health Research Initiative Program (81161120543, ZPJ) and the MRC (GLC).

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Authors and Affiliations

  1. Neurosciences & Mental Health Program, The Hospital for Sick Children, Department of Physiology, University of Toronto, Toronto, Canada

    Zhengping Jia Ph.D.

  2. Centre for Synaptic Plasticity, School of Physiology & Pharmacology, University of Bristol, Bristol, UK

    Graham Collingridge Ph.D.

Authors
  1. Zhengping Jia Ph.D.
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  2. Graham Collingridge Ph.D.
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Correspondence to Zhengping Jia Ph.D. .

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Editors and Affiliations

  1. Neuropharmacology Unit I.N.M. Neuromed, I.N.M. Neuromed, Pozzilli, Isernia, Italy

    Richard Teke Ngomba

  2. Department of Physiology and Biochemistry, University of Malta, Malta, Italy

    Ph.D. Giuseppe Di Giovanni

  3. Neuropharmacology Unit, I.N.M. Neuromed, Pozzilli, Isernia, Italy

    Giuseppe Battaglia

  4. Dipartimento di Fisiologia Umana, Università di Roma, Roma, Italy

    Ferdinando Nicoletti

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Jia, Z., Collingridge, G. (2017). Regulation of Hippocampal mGluR-Dependent Long-Term Depression by GluA2-Dependent Cofilin-Mediated Actin Remodeling. In: Ngomba, R., Di Giovanni, G., Battaglia, G., Nicoletti, F. (eds) mGLU Receptors. The Receptors, vol 31. Humana Press, Cham. https://doi.org/10.1007/978-3-319-56170-7_12

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